Stereotactic body radiation therapy (SBRT) is rapidly emerging as an important tool in the treatment of cancer. SBRT has already made a dramatic clinical impact on the ability to achieve local control for gross deposits of cancer in multiple organ sites. This success, particularly evident in early stage lung cancer patients unfit for surgery, has allowed an absolute reduction in rate of infield recurrence on the order of 50% compared to conventionally fractionated radiotherapy (CFRT). Most of the impressive gains achieved with SBRT have been facilitated by technological innovation: precision targeting with image guidance, sharp dose gradients with 3-D and intensity modulated dosimetry, and management of motion at the time of treatment. While the therapy is increasingly utilized, even in community practices, relatively little is known about the molecular or biological basis of this treatment that uses extremely large daily dose per fraction treatment. SBRT causes unique biological effects on tissue distinct from those observed during the very long history and implementation of conventionally fractionated radiotherapy (CFRT). Mere extrapolation via understanding or modeling of data from CFRT will not properly characterize SBRT or exploit its potential advantages. Specific investigations of a molecular, biological, physiological, and translational nature after SBRT are required for prudent clinical implementation. To fully understand and exploit the mechanisms of focused, high dose irradiation, pre-clinical investigation must be facilitated in a manner that directly mimics clinical delivery, complete with image guidance and conformal dosimetry. The instrument we are seeking is uniquely suited to fulfill these requirements.